Inpharma 1370 - 18 Jan 2003

Thiazide diuretics preferred initialtherapy for hypertension

Thiazide-type diuretics are the preferred initialtherapy for the prevention of cardiovascular disease inpatients with stage 1 or 2 hypertension, reportresearchers from the ALLHAT* study.1

They randomised a total of 33 357 such patients aged≥ 55 years to receive chlorthalidone 12.5–25 mg/day (n= 15 255), amlodipine 2.5–10 mg/day (9048) orlisinopril 10–40 mg/day.** The goal BP in each groupwas < 140/90mm Hg and was achieved throughtitration of the study drug and the addition of open-labelatenolol, reserpine, clonidine or hydralazine whennecessary.

After a mean follow-up of 4.9 years, the primaryoutcome of combined fatal coronary heart disease ornon-fatal myocardial infarction had occurred in 2956patients. There was no significant difference in theincidence of the primary outcome betweenchlorthalidone and amlodipine recipients [relative risk(RR) 0.98; 95% CI 0.9–1.07], or between chlorthalidoneand lisinopril recipients (0.99; 0.91–1.08). Nor did thesecondary outcome of all-cause mortality differ betweenthe treatment groups. However, compared withchlorthalidone recipients, patients in the amlodipinetreatment group had significantly greater 6-year rates ofheart failure (7.7% vs 10.2%, RR 1.38; 95% CI1.25–1.52) and of hospitalised/fatal heart failure (6.5%vs 8.4%, 1.35; 1.21–1.5). Furthermore, compared withchlorthalidone recipients, lisinopril recipients hadsignificantly greater 6-year rates of combinedcardiovascular disease (30.9% vs 33.3%, RR 1.1; 95% CI1.05–1.16), stroke (5.6% vs 6.3%; RR 1.15; 1.02–1.3)and heart failure (7.7% vs 8.7%, RR 1.19; 1.07–1.31). Inaddition, the mean 5-year systolic BP was significantlyhigher among amlodipine and lisinopril recipients,compared with chlorthalidone recipients (134.7mm Hgand 135.9mm Hg vs 133.9mm Hg, respectively).However, the mean 5-year diastolic BP was significantlylower among patients in the amlodipine, compared withchlorthalidone, treatment group (74.6mm Hg vs75.4mm Hg).

According to the researchers, "thiazide-type diureticsshould be considered first for pharmacologic therapy inpatients with hypertension. They are unsurpassed inlowering BP, reducing clinical events, and tolerability,and they are less costly".

In an accompanying editorial, Dr Lawrence Appelfrom the Johns Hopkins University, Baltimore, US,comments that "results from ALLHAT provide definitivedata on one important aspect of hypertensionmanagement–selecting the best initial therapy. Attentionmust now return to other critical issues, specifically,controlling BP among patients with hypertension andpreventing hypertension in the first place."2

* ALLHAT = The Antihypertensive and Lipid-lowering Treatment toPrevent Heart Attack Trial** This study was supported by Pfizer.

1. ALLHAT Officers and Coordinators for the ALLHAT Collaborative ResearchGroup. Major outcomes in high-risk hypertensive patients randomized toangiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic:the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart AttackTrial (ALLHAT). JAMA: the Journal of the American Medical Association 288:2981-2997, 18 Dec 2002.

2. Appel LJ. The verdict from ALLHAT - thiazide diuretics are the preferredinitial therapy for hypertension. JAMA: the Journal of the American MedicalAssociation 288: 3039-3042, 18 Dec 2002.

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Inpharma 18 Jan 2003 No. 13701173-8324/10/1370-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved